Non-alcoholic steatohepatitis with normal aminotransferase values

Table 1 Anthropometric, clinical and laboratory features of all NAFLD cases according to liver enzyme levels n (%)

	According to liver enzyme levels (n = 34)		P
	Normal liver enzyme (n = 9)	Elevated liver enzyme (n = 25)
Age (yr)	52.0 ± 6.16	49.8 ± 6.77	> 0.05
Gender (male/female)	1/8 (11.2/88.8)	10/15 (40/60)	> 0.05
Hepatomegaly	4 (44.4)	7 (28.0)	> 0.05
BMI (kg/m2)
Normal weight	0 (0)	1 (4)	> 0.05
Overweight	0 (0)	2 (8)	> 0.05
Obese	7 (77.8)	20 (80.0)	> 0.05
Morbid obese	2 (22.2)	2 (8.0)	> 0.05
Waist/hip ratio	6 (66.7)	19 (76.0)	> 0.05
Systolic blood pressure (mmHg)1	130 (110-150)	120 (110-180)	> 0.05
Diastolic blood pressure (mmHg)1	76 (60-90)	70 (60-120)	> 0.05
Hypertension	4 (44.4)	12 (48.0)	> 0.05
HDL-Cholesterol (mg/dL)	43.56 ± 7.99	45.52 ± 7.04	> 0.05
Low-HDL level	6 (66.7)	11 (44.0)	> 0.05
Triglycerides (mg/dL)1	187 (43-360)	125 (39-304)	> 0.05
Hypertriglyceridemia	7 (77.8)	8 (32.0)	< 0.05
Fasting glucose (mg/dL)1	101 (73-164)	101 (87-195)	> 0.05
Diabetes	2 (22.2)	6 (24.0)	> 0.05
Impaired glucose tolerance	3 (33.3)	7 (28.0)	> 0.05
Fasting insulin (&mgr;U/mL)1	11.8 (6-23.66)	15.23 (4.76-47.3)	> 0.05
Insulin resistance-HOMA-IR	2 (22.2)	14 (56.0)	> 0.05
AST (IU/L)1	17 (14-29)	49 (33-92)	< 0.05
ALT (IU/L)1	13 (13-33)	81 (32-166)	< 0.05
GGT (IU/L)1	19 (15-33)	42 (15-426)	< 0.05
ALP (IU/L)1	96 (52-113)	81 (51-154)	> 0.05
NASH	7 (77.7)	16 (64.0)	> 0.05
Metabolic syndrome	8 (88.8)	19 (76)	> 0.05

¹Data expressed as median (minimum-maximum); BMI: Body mass index; HDL: High-density lipoprotein; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transpeptidase. Only the prevalence of hyperglyceridemia in NAFLD patients with normal liver enzyme levels was higher than in those with elevated liver enzyme.

Table 2 Features of NASH patients according to high and normal aminotransferase levels n (%)

	NASH cases (n = 23)		P
	Normal aminotransferase levels (n = 7)	Elevated aminotransferase levels (n = 16)
Age (yr)	52.8 ± 5.04	50.44 ± 5.12	> 0.05
Gender (male/female)	1/6 (14.2/85.8)	6/10 (37.5/62.5)	> 0.05
Hepatomegaly	2 (28.5)	5 (31.2)	> 0.05
BMI (kg/m2)
Normal weight	-	-
Overweight	-	-
Obese	6 (85.7)	14 (87.5)	> 0.05
Morbid obese	1 (14.3)	2 (12.5)	> 0.05
Waist/hip ratio	5 (71.4)	12 (75.0)	> 0.05
Systolic blood pressure (mmHg)1	130.0 (110-150)	120 (110-180)	> 0.05
Diastolic blood pressure (mmHg)1	80 (60-90)	70 (60-120)	> 0.05
Hypertension	3 (42.9)	7 (43.8)	> 0.05
HDL-Cholesterol (mg/dL)	43.86 ± 8.97	44.19 ± 4.07	> 0.05
Low-HDL level	4 (57.1)	9 (56.3)	> 0.05
Triglycerides (mg/dL)	183.57 ± 95.82	130.44 ± 59.46	> 0.05
Hypertriglyceridemia	5 (71.4)	5 (31.3)	> 0.05
Fasting glucose (mg/dL)1	101 (73-164)	102.83 (87-195)	> 0.05
Diabetes	2 (28.6)	4 (25.0)	> 0.05
Impaired glucose tolerance	3 (42.9)	6 (37.5)	> 0.05
Fasting insulin (&mgr;U/mL)	11.8	13.96	> 0.05
Insulin resistance-HOMA-IR	1 (14.3)	9 (56.3)	> 0.05
AST (IU/L)1	18 (14-29)	46 (33-92)	< 0.05
ALT (IU/L)1	21 (15-39)	77 (32-158)	< 0.05
GGT (IU/L)1	21 (15-33)	40 (16-119)	< 0.05
ALP (IU/L)1	96 (52-111)	78.5 (55-152)	> 0.05
Metabolic syndrome	6 (85.7)	12 (75.0)	> 0.05

¹Data expressed as median (minimum-maximum); BMI: Body mass index; HDL: High-density lipoprotein; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transpeptidase. There was no difference between the features of NASH patients with high and normal aminotransferase levels.

Table 3 Features of NASH patients with high and normal aminotransferase levels according to the presence of metabolic syndrome n (%)

	NASH cases (n = 23)		P
	With metabolic syndrome (n = 18)	Without metabolic syndrome (n = 5)
Average age (yr)	52.7 ± 4.34	45.4 ± 3.20	< 0.05
Gender (male/female)	3/15 (16.7/83.3)	4/1 (80.0/20.0)	< 0.05
Hepatomegaly	5 (29.4)	2 (50)	> 0.05
BMI (kg/m2)
Normal weight	-	-
Overweight	-	-
Obese	15 (83.3)	5 (100)	> 0.05
Morbid obese	3 (16.7)	0 (0)	> 0.05
Waist/hip ratio	13/(72.2)	4 (80.0)	> 0.05
Hypertension	10 (55.6)	0 (0)	< 0.05
Low HDL level	13 (72.2)	0 (0)	< 0.05
Hypertriglyceridemia	10 (55.6)	0 (0)	< 0.05
Diabetes	5 (27.8)	1 (20.0)	> 0.05
Impaired glucose tolerance	8 (44.4)	1 (20.0)	> 0.05
Insulin resistance-HOMA-IR	6 (75)	4 (80.0)	> 0.05
AST (IU/L)	38. 06 ± 16.63	53.60 ± 27.04	> 0.05
ALT (IU/L)	57.39 ± 32.127	84.8 ± 49. 37	> 0.05
AST/ALT > 1	3 (16.6)	1 (20.0)	> 0.05
GGT (IU/L)1	29.5 (15-83)	33 (16-119)	> 0.05
ALP (IU/L)	83.44 ± 18.19	98.20 ± 38.78	> 0.05

¹Data expressed as median (minimum-maximum); BMI: Body mass index; HDL: High-density lipoprotein; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transpeptidase. There were significant differences between NASH cases with or without metabolic syndrome according to average age, gender and the presence of hypertension, low-HDL level and hypertriglyceridemia.

Table 4 Liver histology according to the level of liver enzymes in all NAFLD cases n (%)

Liver histology	All NAFLD patients
	Patients with normal aminotransferase levels (n = 9)	Patients with elevated aminotransferase levels (n = 25)
Steatosis
Mild	5 (55.5)	12 (48.0)
Moderate	3 (33.3)	7 (28.0)
Severe	1 (11.2)	6 (24.0)
Necroinflammation
Absent	2 (22.2)	9 (36.0)
Mild	4 (44.4)	3 (12.0)
Moderate	2 (22.2)	10 (40.0)
Severe	1 (11.2)	3 (12.0)
Fibrosis
Absent	7 (77.7)	16 (64.0)
Perisinusoidal/pericellular	2 (22.3)	6 (24.0)
Periportal	0 (0)	2 (8.0)
Bridging	0 (0)	1 (4.0)

Due to the small number of patients, statistical evaluation and P values were not available. Patients with elevated liver enzyme levels seemed to have more sever liver histology than those with normal liver enzyme levels, but this was not statistically significant.

Table 5 Liver histology according to AST/ALT ratio values in all NAFLD cases n (%)

Liver histology	All NAFLD patients
	Patients with AST/ALT > 1 (n = 6)	Patients with AST/ALT < 1 (n = 28)
Steatosis
Mild	2 (33.3)	15 (53.5)
Moderate	2 (33.3)	7 (25.0)
Severe	2 (33.4)	6 (21.5)
Necroinflammation
Absent	3 (50.0)	3 (10.7)
Mild	0 (0)	12 (42.9)
Moderate	1 (16.7)	11 (39.2)
Severe	2 (33.3)	2 (7.2)
Fibrosis
Absent	4 (66.6)	18 (64.3)
Perisinusoidal/pericellular	1 (16.6)	7 (25.0)
Periportal	0 (0)	3 (10.7)
Bridging	1 (16.6)	0 (0)

Due to the small number of patients statistical evaluation and P values were not available. There were no significant differences between patient groups according to AST/ALT ratio.

Table 6 Comparison between patients with NASH and without NASH according to anthropometric, clinical and laboratory features n (%)

	All NAFLD patients		P
	Patients with NASH (n = 23)	Patients without NASH (n = 11)
Age (yr)	51.17 ± 5.11	48.82 ± 9.05	> 0.05
Gender: male/female	7/16 (30.4/69.6)	4/7 (36.4/63.6)	> 0.05
Hepatomegaly	7 (29.2)	4 (36.4)	> 0.05
Obesity (BMI ≥ 30)	23 (100)	8 (72.7)	< 0.05
Waist/hip ratio	17 (63.6)	7 (73.9)	> 0.05
Systolic blood pressure (mmHg)1	120 (110-180)	130 (110-180)	> 0.05
Diastolic blood pressure (mmHg)1	70 (65-110)	70 (60-120)	> 0.05
Hypertension	10 (45.5)	6 (60)	> 0.05
HDL-Cholesterol (mg/dL)	44.09 ± 5.77	46.91 ± 9.66	> 0.05
Low-HDL level	13 (56.5)	4 (36.4)	> 0.05
Triglycerides (mg/dL)	146.61 ± 74.43	174.18 ± 83.85	> 0.05
Hypertriglyceridemia	10 (43.5)	5 (45.5)	> 0.05
Fasting glucose (mg/dL)1	102.33 (73-195)	100 (83-125)	> 0.05
Diabetes	6 (26.1)	2 (18.2)	> 0.05
Impaired glucose tolerance	9 (39.1)	1 (9.1)	> 0.05
Fasting insulin (&mgr;U/mL)1	13.44 (4.76-47.3)	16.60 (6-21.80)	> 0.05
Insulin resistance-HOMA-IR	13 (81.3)	6 (66.7)	> 0.05
AST (U/L)1	40 (14-92)	51 (14-78)	> 0.05
ALT (U/L)1	67 (15-158)	82 (13-166)	> 0.05
GGT (U/L)1	33 (15-119)	43 (15-426)	> 0.05
ALP (U/L)1	81 (52-152)	81 (51-154)	> 0.05
AST/ALT > 1	4 (17.3)	2 (18.1)	> 0.05
Metabolic syndrome	18 (78.3)	9 (81.8)	> 0.05

¹Data expressed as median (minimum-maximum); BMI: Body mass index; HOMA: Homeostasis model assessment; HDL: High-density lipoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma glutamyl transpeptidase. There was a significant difference between patients with or without NASH according to the presence of obesity only.